Dynamic simulations on the arachidonic acid metabolic network

doi:10.1371/journal.pcbi.0030055

CORC > 化学研究所 > 中国科学院化学研究所

	Dynamic simulations on the arachidonic acid metabolic network
	Yang, Kun ; Ma, Wenzhe ; Liang, Huanhuan ; Qi Ouyang ; Tang, Chao ; Lai, Luhua
刊名	PLOS COMPUTATIONAL BIOLOGY
	2007-03-01
卷号	3 期号:3 页码:523-530
ISSN号	1553-734X
DOI	10.1371/journal.pcbi.0030055
英文摘要	Drug molecules not only interact with specific targets, but also alter the state and function of the associated biological network. How to design drugs and evaluate their functions at the systems level becomes a key issue in highly efficient and low-side-effect drug design. The arachidonic acid metabolic network is the network that produces inflammatory mediators, in which several enzymes, including cyclooxygenase-2 (COX-2), have been used as targets for anti-inflammatory drugs. However, neither the century-old nonsteriodal anti-inflammatory drugs nor the recently revocatory Vioxx have provided completely successful anti-inflammatory treatment. To gain more insights into the anti-inflammatory drug design, the authors have studied the dynamic properties of arachidonic acid (AA) metabolic network in human polymorphous leukocytes. Metabolic flux, exogenous AA effects, and drug efficacy have been analyzed using ordinary differential equations. The flux balance in the AA network was found to be important for efficient and safe drug design. When only the 5-lipoxygenase (5-LOX) inhibitor was used, the flux of the COX-2 pathway was increased significantly, showing that a single functional inhibitor cannot effectively control the production of inflammatory mediators. When both COX-2 and 5-LOX were blocked, the production of inflammatory mediators could be completely shut off. The authors have also investigated the differences between a dual-functional COX-2 and 5-LOX inhibitor and a mixture of these two types of inhibitors. Their work provides an example for the integration of systems biology and drug discovery.
语种	英语
出版者	PUBLIC LIBRARY SCIENCE
WOS记录号	WOS:000246191000018
内容类型	期刊论文
源URL	[http://ir.iccas.ac.cn/handle/121111/60737]
专题	中国科学院化学研究所
通讯作者	Lai, Luhua
作者单位	1.Peking Univ, Beijing Natl Lab Mol Sci, State Key Lab Struct Chem Unstable & Stable Speci, Coll Chem & Mol Engn, Beijing 100871, Peoples R China 2.Peking Univ, Ctr Theoret Biol, Beijing 100871, Peoples R China
推荐引用方式 GB/T 7714	Yang, Kun,Ma, Wenzhe,Liang, Huanhuan,et al. Dynamic simulations on the arachidonic acid metabolic network[J]. PLOS COMPUTATIONAL BIOLOGY,2007,3(3):523-530.
APA	Yang, Kun,Ma, Wenzhe,Liang, Huanhuan,Qi Ouyang,Tang, Chao,&Lai, Luhua.(2007).Dynamic simulations on the arachidonic acid metabolic network.PLOS COMPUTATIONAL BIOLOGY,3(3),523-530.
MLA	Yang, Kun,et al."Dynamic simulations on the arachidonic acid metabolic network".PLOS COMPUTATIONAL BIOLOGY 3.3(2007):523-530.